Studies Support Antibiotics from the Start for Otitis Media

Action Points

Note that current guidelines recommend initial observation rather than immediate antimicrobial therapy for the management of acute otitis media in selected children.

Point out, however, that these two studies indicate that children with acute otitis media benefit from immediate antimicrobial treatment as compared with placebo, although they have more side effects.

Children with otitis media had more durable symptom resolution and a 70% to 80% lower rate of clinical failure when they started antibiotic therapy at diagnosis, as compared with observation, data from a U.S. multicenter trial showed.

Symptoms disappeared at a similar pace in both groups. However, patients treated with immediate amoxicillin-clavulanate had significantly lower rates of clinical failure on days four and five and on days 10 to 12 (P<0.001), as reported in the Jan. 13 issue of the New England Journal of Medicine.

Similar results, reported in the same issue, emerged from a randomized trial conducted in Finland: Immediate antibiotic therapy was associated with a 62% reduction in the rate of treatment failure and an 81% reduction in the need for rescue treatment.

Both studies showed significantly higher rates of diarrhea in association with amoxicillin-clavulanate therapy.

The risk of adverse effects and the potential for contributing to antibiotic resistance led to a cautious assessment of the results by U.S. investigators.

"The benefit must be weighed against concern not only about the side effects of the medication but also about the contribution of antimicrobial treatment to the emergence of bacterial resistance," Alejandro Hoberman, MD, of Children's Hospital of Pittsburgh, and co-authors wrote in conclusion.

"These considerations underscore the need to restrict treatment to children whose illness is diagnosed with the use of stringent criteria."

Clinical trials have shown high rates of spontaneous improvement in otitis media, leading many European nations to support observation, or watchful waiting, as the preferred initial approach to management of the condition. In contrast, routine antibiotic therapy has been the U.S. standard, authors of the U.S. report noted in their introduction.

Since 2004, the American Academy of Pediatrics and the American Academy of Family Physicians have endorsed watchful waiting as an option for children 6 to 23 months of age who have nonsevere illness and an uncertain diagnosis (Pediatrics 2004; 113: 1451-1465).

Clinical trials often cited in support of watchful waiting had several notable limitations: lack of stringent diagnostic criteria, inclusion of few very young children, and use of antibiotics with limited efficacy or at suboptimal doses. Moreover, rates of spontaneous remission were not uniform.

"Therefore, for children with acute otitis media, the circumstances in which immediate antimicrobial treatment is the preferred strategy have remained unclear," Hoberman and co-authors wrote.

In an effort to address the limitations, investigators enrolled 291 children ages 6 to 23 months and who had received at least two doses of pneumococcal conjugate vaccine.

All study participants met three criteria for a diagnosis of acute otitis media (in addition to symptom onset within the past 48 hours):

Parent rating of 3 or higher on the Acute Otitis Media Severity of Symptoms (AOS-SOS) scale

Presence of middle-ear effusion

Moderate or marked bulging of the tympanic membrane or slight bulging accompanied by otalgia or marked erythema

The children were randomized to a 10-day course of amoxicillin-clavulanate or matching placebo. Parents also could give acetaminophen for symptom relief.

The primary endpoints were symptomatic response (by AOS-SOS scores) and clinical failure, defined as lack of substantial improvement in or worsening of symptoms before the day four-five visit and failure to achieve complete or nearly complete resolution of symptoms and otoscopic signs by day 10 to 12.

Hoberman and co-authors reported that 35% of the antibiotic group had initial symptom resolution by day two, 61% by day four, and 80% by day seven. Corresponding figures for the observation group were 28%, 54%, and 74% (P=0.14).

Rates of sustained symptom resolution on the same days were 20%, 41%, and 67% with amoxicillin-clavulanate versus 14%, 36%, and 53% with observation (P=0.04).

Mean symptom scores over the first seven days also were significantly lower in the antibiotic arm (P=0.02).

Clinical failure rates before the day four-five visit were 4% with antibiotics and 23% with observation, increasing to 16% versus 51% by day 10 to 12 (P<0.001 for both comparisons).

Diarrhea occurred in 36 (25%) of the children in the antibiotic group versus 22 (15%) of those in the placebo group (P=0.05). Additionally, diaper-area rash was more common with antibiotic therapy (51% versus 35%, P=0.008).

The Finnish study involved 319 children ages 6 to 35 months, with a diagnosis of otitis media by standardized criteria that included clinical, otoscopic, and tympanometric examinations. The patients were randomized to a seven-day course of amoxicillin-clavulanate or placebo.

The primary endpoint was time to treatment failure from first dose to end-of-treatment evaluation on day eight. The definition of treatment failure comprised the patient's overall condition, including adverse events and otoscopic signs of acute otitis media, Paula A. Tähtinen, MD, of Turku University Hospital, and co-authors reported.

Treatment failure occurred in 18.6% of the antibiotic group versus 44.9% of the placebo group (P<0.001).

The difference had become apparent at the first follow-up on day three, when treatment failure had occurred in 13.7% of the antibiotic group and 25.3% of the placebo group.

Treatment with amoxicillin-clavulanate was associated with a hazard ratio of 0.38 for treatment failure versus placebo (P<0.001).

The authors reported that 6.8% of the antibiotic group and 33.5% of the placebo group required rescue medication (P<0.001).

As in the U.S. study, diarrhea occurred significantly more often in the antibiotic arm (47.8% versus 26.6%, P<0.001), as did rash (8.7% versus 3.2%, P=0.04).

Collectively, the two studies provided a clear answer to an unresolved clinical question, Jerome Klein, MD, of Boston University Medical Center, wrote in an accompanying editorial.

"Is acute otitis media a treatable disease? The investigators in Pittsburgh and Turku have provided the best data yet to answer the question, and the answer is yes," Klein wrote. "More young children with a certain diagnosis of acute otitis media recover more quickly when they are treated with an appropriate antimicrobial agent."

The U.S. study was supported by the National institute of Allergy and Infectious Diseases. The Finnish study was supported by multiple noncommercial foundations, societies, and organizations.

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